MULTIDOSE VET. injekční roztok pro psy a kočky (buprenorphinum 0,3mg/ml) 10 ml

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1 VETERGESIC MULTIDOSE VET injekční roztok pro psy a kočky (buprenorphinum 0,3mg/ml) 10 ml Orion Oyj organizační složka, Zelený pruh 95/97, Praha, tel.: , fax: Část B

2 je opioidem pro rutinní použití u psů a koček je opioidem pro rutinní použití u psů a koček 1) Buprenorfin (0,01-0,02 mg/kg) je parciálním μ-agonistou. Je nejčastěji používaným opioidem v malé praxi ve Velké Británii, ostatních evropských zemích, Austrálii i jižní Africe. V klinických studiích vykazoval lepší analgezii než několik jiných opioidů a jeví se být vysoce vhodným pro perioperativní management bolesti u koček. 3) Ve většině preklinických nociceptivních testů (testů bolestivosti) vykazoval buprenorfin výborný analgetický efekt, když jeho antinociceptivní potence (analgetická schopnost) byla 20-40x vyšší, než vykazoval morfin. Robertson SA, Taylor PM. J Feline Med Surg Oct; 6(5): REVIEW ARTICLE: Pain management in cats - past, present and future. Part 2. Treatment of pain - clinical pharmacology. Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL, USA. Opioids have an unjustifi ed reputation for causing mania in cats, but with refi nements in dosing they are now used successfully in this species. The mu-opioid agonists are generally considered the best analgesics. Morphine ( mg/kg) is effective in a clinical setting. Methadone (up to 0.5 mg/kg) has a similar profi le to morphine. Pethidine (Demerol, meperidine; 2-5 mg/kg) is a useful analgesic with a faster onset but shorter duration of action than morphine. Oxymorphone and hydromorphone ( mg/ kg) are widely used in the USA. These opioids are more potent (up to 10 times), and longer acting than morphine in cats. Butorphanol ( mg/kg) is a mu-opioid antagonist that produces its analgesic actions through kappa agonist activity. It rapidly reaches a ceiling effect, is short acting and is a weaker analgesic than pure mu opioids. Buprenorphine ( mg/kg), a partial mu-agonist, is the most popular opioid used in small animal practice in the UK, other parts of Europe, Australia and South Africa. In clinical studies it has produced better analgesia than several other opioids and appears to be highly suitable for perioperative pain management in cats. NSAIDs are also used in cats for pain management, although cats metabolise these differently from other species. With appropriate dosing, carprofen (1-4 mg/ kg) and meloxicam (0.3 mg/kg) have proved highly effective with few side effects. The use of ketoprofen (2 mg/kg), tolfenamic acid (4 mg/kg) and vedaprofen (0.5 mg/kg) has been reported in cats. Other less traditional analgesics such as ketamine, medetomidine and local anaesthetics are also used for clinical pain management. The transmucosal, transdermal and epidural routes offer novel methods for administration of analgesic drugs and have considerable potential for improving techniques in feline pain management. Cowan A. Int J Clin Pract Suppl Feb;(133):3-8; discussion Buprenorphine: new pharmacological aspects. Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. Buprenorphine is an opioid analgesic, derived from thebaine. Buprenorphine was initially classifi ed as a mixed agonist-antagonist analgesic or a narcotic antagonist analgesic. The work of Martin et al (1976) on the animal model of the chronic spinal dog substantiated the substance s action as partial agonist at the mu-opioid receptor. These fi ndings were underscored by the substance s general pharmacological profi le. Further, buprenorphine was one of the fi rst narcotic analgesics to be assessed for its abuse liability in humans. The lower abuse liability of the drug in humans soon turned it into a widely used therapeutic agent in patients with opioid dependence. Interest in buprenorphine spanning more than 30 years has been attributed to its unique pharmacological characteristics, including moderate intrinsic activity, high affi nity to and slow dissociation from mu-opioid receptors. Early pharmacological studies demonstrated buprenorphine s strong binding to opioid receptors, and an inverted U-shaped dose-response curve in rodents. In the rat paw formalin test, although buprenorphine demonstrated a bell-shaped doseresponse curve against an acute noxious stimulus, it showed a classic sigmoidal curve in the later phase of the assay. In most preclinical antinociceptive tests, buprenorphine was shown to be fully effi cacious, with an antinociceptive potency 25 to 40 times higher than morphine. A ceiling effect for respiratory depression (but not for analgesia) has been demonstrated in humans. Current studies are focusing on norbuprenorphine, an N-dealkylated metabolite of buprenorphine. Norbuprenorphine is a likely contributor to the overall pharmacology of buprenorphine; in the mouse writhing test, norbuprenorphine provides antinociceptive effi cacy similar to buprenorphine, with analgesic activity shown to be dose-dependent. 2) Doporučení týkající se terapeutického používání konkrétních analgetik by ideálně měla být založena na přímém potvrzení jejich klinické účinnosti. Jestliže takové studie nejsou k dispozici, lze pro predikci klinicky efektivních dávek využít výsledky nociceptivních testů (testů bolestivosti). Nicméně např. při testování odezvy na bolestivý podnět může mít výsledná křivka malý klinický význam. Prakticky se totiž potvrdilo, že když se analgezie buprenorfinem jeví nedostatečná, lze podat další dávku buprenorfinu. Jestliže se poté zdá, že buprenorfin stále není dostatečným analgetikem, může tomu být následkem toho, že vyšší dávkou látky již nedosáhneme většího účinku (ceiling effect), nebo individuální interakcí s jinými analgetiky (čistí μ-agonisté). V tomto případě lze pro analgezii využít nesteroidní antiflogistika nebo lokální anestetika. Roughan JV, Flecknell PA. Lab Anim Jul;36(3): Buprenorphine: a reappraisal of its antinociceptive effects and therapeutic use in alleviating post-operative pain in animals. Comparative Biology Centre, Medical School, Framlington Place, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK. Buprenorphine has been widely used for post-operative analgesia in laboratory animals. Clinical effi cacy has been demonstrated in both subjective and objective pain assessment schemes, however doubts have been expressed as to its value as an analgesic. Initial dosage recommendations were based on analgesiometric studies. It is unlikely, however, that the pain elicited in analgesiometric tests is comparable to post-operative pain. This has resulted in recommendations of excessive dose rates and inappropriate clinical indications. Studies involving tests of the effi cacy of buprenorphine for alleviating behavioural or other signs of tonic (post-surgical) pain provide a more appropriate estimation of the analgesic capabilities of the drug. However, buprenorphine also has major effects upon the behaviour of normal (unoperated) animals, and this makes assessments of effi cacy diffi cult with some of the systems used for scoring clinical pain. Nevertheless, our most recent studies of the effects of buprenorphine upon pain-related behaviours in rats support the view that it is an effective post-operative analgesic. This short review critically reappraises the role of buprenorphine in this capacity and discusses a rational approach to the relief of pain in laboratory animals. We conclude that buprenorphine remains a valuable agent for pain relief in a wide range of animal species when used in an appropriate manner.

3 poskytuje silnou postoperativní opioidní analgezii poskytuje silnou postoperativní opioidní analgezii 1) Postoperativní analgezie se po provedené artrotomii u psů při preoperativním podání morfinu i buprenorfinu jevila stejně efektivní po dobu 7 hodin. 52 psů. Brodbelt DC, Taylor PM, Stanway GW. J Vet Pharmacol Ther Aug;20(4): A comparison of preoperative morphine and buprenorphine for postoperative analgesia for arthrotomy in dogs. Department of Clinical Veterinary Medicine, Cambridge University, UK. The aim of this study was to compare morphine with the partial agonist, buprenorphine, for postoperative analgesic effects, when administered preoperatively for elective arthrotomy in dogs. Fifty two dogs were anaesthetized for stifl e, elbow, or hock arthrotomy. The dogs were premedicated 30 min prior to induction of anaesthesia with 0.03 mg/kg acepromazine intramuscularly, and either 0.3 mg/kg morphine or 0.01 mg/kg buprenorphine intramuscularly (allocated randomly). Anaesthesia was induced with thiopentone and maintained with halothane in an oxygen/nitrous oxide mixture. Pain and sedation were assessed preoperatively, and 0.5, 1, 2, 3, 5, and 7 h after the halothane was switched off, with a visual analogue scale scoring system. Pain scores did not differ signifi cantly (morphine group median postoperative score from 30 to 40 mm, buprenophine group median postoperative score from 36 to 43 mm) and analgesia was considered adequate in the majority of cases (score less than 40 mm). Morphine produced signifi cantly more sedation at 0.5 h after anaesthesia only. It was concluded that both opioids are equally suitable analgesics for postoperative analgesia for the elective arthrotomy in dogs. 2) U koček po operaci bylo zřejmé, že buprenorfin v dávce 0,01 mg/kg poskytoval lepší postoperativní analgezii než morfin v dávce 0,1 mg/kg. 32 koček. GW Stanway, PM Taylor, DC Brodbelt Vet Anaesth Analg, 2002, 29, A preliminary investigation comparing pre-operative morphine and buprenorphine for postoperative analgesia and sedation in cats. Objective: To compare the postoperative analgesic and sedative properties of buprenorphine and morphine in cats. Study Design Prospective, randomized, blinded study. Animals Thirty-two domestic cats undergoing surgery. Methods Cats received pre-anaesthetic medication with acepromazine (0.05 mg kg 1) given intramuscularly and were randomly allocated to group M and given morphine (0.1 mg kg 1) intramuscularly (IM) or to group B and given buprenorphine (0.01 mg kg 1) IM. Anaesthesia was induced with propofol and maintained with halothane in oxygen and nitrous oxide. Pain and sedation scores using visual analogue scales, and heart and respiratory rates, were measured immediately before, and 30, 60, 120, 180, 300 and 420 minutes after anaesthesia. Results Pain scores were signifi cantly lower at 60, 120 and 180 minutes after anaesthesia in group B. Group B also had higher heart rates at 30 minutes. There were no other statistically signifi cant differences between the groups. Clinical relevance Buprenorphine (0.01 mg kg 1) appeared to provide better postoperative analgesia than morphine (0.1 mg kg 1) and may also have a longer duration of action. surgery) demonstrated post-operative hyperalgesia in all groups; this hyperalgesia was least in the pre-operative pethidine group. In summary, this study clearly shows pethidine to be an effective analgesic in dogs, albeit of short duration of action, when administered post-operatively, and, importantly, that it has a positive Steagall PV, Mantovani FB, Taylor PM, Dixon MJ, Luna SP. Vet J Nov;182(2): Epub 2008 Aug 8. Dose-related antinociceptive effects of intravenous buprenorphine in cats. Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI , USA. The dose-related antinociceptive effects of intravenous (IV) buprenorphine were evaluated in cats. Thermal (TT) and mechanical threshold (MT) devices were used for nociceptive stimulation. After baseline threshold recordings, buprenorphine was benefi t in terms of post-operative outcome measures, when administered pre-operatively, possibly as a result of blocking or preventing the development of central sensitisation following surgical stimulation.kg 1) and may also have a longer duration of action. 4) Intravenozní podání jakýchkoli testovaných dávek buprenorfinu kočkám vedlo k rychlejšímu nástupu účinku, než byl kdy zaznamenám v předchozích studiích. Nebyla zanamenána žádná na dávce závislá odezva na teplotní stimulaci. Analgezie vůči mechanickým stimulům vykazovala závislost na dávce s většími dávkami byla antinocicepce silnější a trvala déle. Všechny dávky navozovaly u koček mírně euforické chování, které mohlo interferovat s posuzováním reakcí na podněty. Na základě této studie by pro klinickou praxi měla být u koček používána dávka buprenorfinu 0,02 mg/kg intravenozně. 8 koček. SPC DOG: For further pain relief, repeat if necessary after 3-4 hours with 10 microgram per kg or 5-6 hours with administered IV (0.01, 0.02 or 0.04 mg/kg; B1, B2 and B4, respectively) in a randomised, blinded and cross-over study. Data were analysed by ANOVA (P<0.05) using 95% confi dence intervals (CI). TT increased 15, 30, 45 min and 1 (5.2+/-2.7 degrees C), 2, 3 and 4 h after B1; 15, 30, 45 min and 1 (5.1+/-3.9 degrees C) and 2 h after B2, and 15, 30, 45 min and 1 (5.4+/-3.3 degrees C), 2, 3, 6 and 8 h after B4. MT increased 15 and 45 min after B2 (260+/-171 mmhg), and 30 (209+/-116 mmhg) and 45 min and 1 and 2 h after B4. At 45 min, MT values were signifi cantly higher after B2 compared to B1 (P<0.05). With MT, B2 and B4 produced more antinociception and longer duration of action than B1, respectively. No dose response to thermal stimulation was detected. 5) Buprenorfin může být opakovaně reaplikován k dosažení maximální analgezie. 20 microgram per kg CAT: repeated if necessary, once, after 1-2 hours 3) Preoperativní podání opiátů může mít pozitivní dlouhodobý efekt na vyblokování nebo prevenci centrální senzibilizace vyvolané chirurgickou stimulací. Pes. 6) Pro dovršení maximální postoperativní analgezie je vhodné aplikaci opakovat. 28 psů. Lascelles BD, Cripps PJ, Jones A, Waterman AE. Pain Dec;73(3): Post-operative central hypersensitivity and pain: the pre-emptive value of pethidine for ovariohysterectomy. Department of Clinical Veterinary Science, Langford House, Bristol, UK. Objective: To compare the postoperative analgesic and sedative The effect of timing of analgesic drug administration on the severity of post-operative pain was investigated in dogs undergoing ovariohysterectomy using both subjective visual assessment scoring systems (VAS) and objective mechanical nociceptive threshold measurements using a novel handheld anti-nociceptiometric device. Forty dogs undergoing routine elective ovariohysterectomy were included in a randomised and double-blind study and assigned to one of three groups: (i) pre-operative analgesics; (ii) post-operative analgesics; (iii) no analgesics (saline injections). The analgesic used was pethidine (a short acting predominantly mu-opioid agonist), at a dose of 5.0 mg/kg (intramuscular). The post-operative administration of pethidine resulted in signifi cantly higher sedation scores and signifi cantly lower pain scores in the early post-operative period, but the dogs given pethidine pre-operatively had signifi cantly lower pain scores than both the other groups at 8, 12 and 20 h post-extubation (P < 0.01, ANOVA). Mechanical thresholds measured at the distal tibia demonstrated the development of allodynia at 12 and 20 h post-extubation, and this was signifi cantly prevented by the pre- (P < 0.01 at 12 h, P < 0.05 at 20 h, Kruskal-Wallis and post hoc Dunn s), but not by the post-operative administration of pethidine. Mechanical nociceptive thresholds measured at the ventral midline (site of Slingsby LS, Taylor PM, Waterman-Pearson AE. Vet Rec Nov 18;159(21): Effects of two doses of buprenorphine four or six hours apart on nociceptive thresholds, pain and sedation in dogs after castration. School of Clinical Veterinary Science, University of Bristol, Langford House, Langford, Bristol BS40 5DU Twenty-eight dogs were randomly allocated into two groups. They were premedicated with either 10 or 20 microg/kg buprenorphine and 0.05 mg/kg acepromazine administered intramuscularly, and then anaesthetised with intravenous thiopentone to effect and maintained with isofl urane in 100 per cent oxygen. The dogs underwent routine castration, and a second dose of 10 microg/ kg buprenorphine was administered four hours after the fi rst or 20 microg/kg six hours after the fi rst dose. Levels of pain and sedation were scored on a visual analogue scale and in terms of the dogs requirement for rescue analgesia, and mechanical nociceptive thresholds were measured at the hock and wound at premedication and one, two, three, four, fi ve, six, seven, 10 and 21 to 22 hours later. Pain scores were low in both groups, with a trend for lower scores in the high dose group; administration of the second dose of buprenorphine further decreased the pain scores. Buprenorphine produced good preoperative sedation and the level of sedation decreased over time after surgery. Administration of the second high dose of buprenorphine did not increase the level of sedation. Both doses of buprenorphine prevented hyperalgesia at the wound and hock postoperatively. Three dogs given the low dose and one dog given the high dose required rescue analgesia with carprofen.

4 poskytuje dlouhotrvající opioidní analgezii je určen pro kočky i psy 1) Teplotní práh byl u koček zvýšený 4-12 hodin po aplikaci buprenorfinu a 4-6 hodin po aplikaci morfinu. 8 koček. 1) Kombinace buprenorfinu a acepromazinu je hemodynamicky dobře tolerována. Podání 5-10 násobné dávky vedlo u zdravých psů k markantní sedaci, avšak nedošlo k podstatnému zhoršení kardiorespiračních funkcí. 11 psů. Robertson SA, Taylor PM, Lascelles BD, Dixon MJ. Vet Rec Oct 11;153(15): Changes in thermal threshold response in eight cats after administration of buprenorphine, butorphanol and morphine. Thermal thresholds were measured in eight cats after the intramuscular administration of morphine (0.2 mg/kg), buprenorphine (0.01 mg/kg) or butorphanol (0.2 mg/kg), doses commonly used in clinical practice; 0.9 per cent saline (0.3 ml) was injected as a control. Groups of six cats were used and each cat participated in at least two treatments, according to a randomised design. The investigator was blinded to the treatments. The thermal thresholds were measured with a testing device developed specifi cally for cats, and measurements were made before and fi ve, 30, 45 and 60 minutes and two, four, six, 12 and 24 hours after the injections. There was no signifi cant change in thermal threshold after the injection of saline. With butorphanol, the threshold was increased only at fi ve minutes after the injection and was decreased two hours after the injection; with morphine it was increased from between four and six hours after the injection, and with buprenorphine it was increased from between four and 12 hours after the injection. Stepien RL, Bonagura JD, Bednarski RM, Muir WW 3rd Am J Vet Res Jan;56(1): Cardiorespiratory effects of acepromazine maleate and buprenorphine hydrochloride in clinically normal dogs. Cardiorespiratory effects of the combination of acepromazine maleate (ACP) 0,1 mg/kg and buprenorphine hydrochloride (BPN), cumulative doses 0,005, 0,01 and 0,1 mg/kg) were studied in 11 healthy, conscious dogs. Sedation level was further increased by administration of Buprenorfi ne at the lowest dose. The combination of ACP and BPN resulted in good to excellent sedation, but further depressed ventricular function. Results of this study indicate that the combination of ACP and BPN in clinically relevant doses is well tolerated hemodynamically. Addition of 10 times the usual clinical dose led to marked sedation, but no substantial deterioration in cardiorespiratory function in these healthy dogs. We have used this combination of drugs in more than 300 dogs. A dosage range of 0.03 to 0.05 mg oc ACP/kg and 0,0075 to 0,01 mg of BPN/kg, mixed and administered IV, has proven to be satisfactory in our experience. 2) Efekt buprenorfinu trvá u koček 8 hodin po jeho podání. 8 koček. Steagall PV, Taylor PM, Brondani JT, Luna SP, Dixon MJ, Ferreira TH. Vet Anaesth Analg Sep;34(5): Effects of buprenorphine, carprofen and saline on thermal and mechanical nociceptive thresholds in cats. Department of Veterinary Surgery and Anaesthesiology, Faculty of Veterinary Medicine and Animal Science, UNESP, Botucatu, São Paulo, Brazil. Erratum in: Vet Anaesth Analg Nov;34(6):450. OBJECTIVE: To evaluate a prototype pressure stimulus device for use in the cat and to compare with a known thermal threshold device. ANIMALS: Eight healthy adult cats weighing between 3.0 and 4.9 kg. METHODS: Pressure stimulation was given via a plastic bracelet taped around the forearm. Three 2.4 mm diameter ball bearings, in a 10-mm triangle, were advanced against the craniolateral surface of the antebrachium by manual infl ation of a modifi ed blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was also tested. Stimuli were stopped if they reached 55 degrees C or 450 mmhg without response. After four pressure and thermal threshold baselines, each cat received SC buprenorphine 0.01 mg kg(-1), carprofen 4 mg kg(-1) or saline 0.3 ml in a three period cross-over study with a 1-week interval. The investigator was blinded to the treatment. Measurements were made at , 0.75, 1, 2, 3, 4, 6, 8, and 24 hours after injection. Data were analyzed by using ANOVA. RESULTS: There were no signifi cant changes in thermal or pressure threshold after administration of saline or carprofen, but thermal threshold increased from 60 minutes until 8 hours after administration of buprenorphine (p < 0.05). The maximum increase in threshold from baseline (DeltaT(max)) was 3.5 +/- 3.1 degrees C at 2 hours. Pressure threshold increased 2 hours after administration of buprenorphine (p < 0.05) when the increase in threshold above baseline (DeltaP(max)) was 162 +/- 189 mmhg. CONCLUSIONS AND CLINICAL RELEVANCE: This pressure device resulted in thresholds that were affected by analgesic treatment in a similar manner but to a lesser degree than the thermal method. Pressure stimulation may be a useful additional method for analgesic studies in cats. 2) Vliv buprenorfinu na kardiovaskulární systém byl v této studii signifikantní, avšak nikoli dostatečně významný, aby měl u zdravých psů klinický význam. 6 psů. Martinez EA, Hartsfield SM, Melendez LD, Matthews NS, Slater MR. Am J Vet Res Nov;58(11): Cardiovascular effects of buprenorphine in anesthetized dogs. OBJECTIVE: To determine the cardiovascular effects of buprenorphine in isofl urane- and halothane-anesthetized dogs. ANI- MALS: 6 healthy adult hound-type dogs given buprenorphine (16 micrograms/kg of body weight, i.v.) or isovolumetric 5% dextrose solution during anesthesia with isofl urane or halothane. PROCE- DURE: Each dog was anesthetized 4 times, with a minimum of 10 days between episodes. Anesthesia was induced with isofl urane or halothane in O2 by mask, and was maintained with 1.9% isoflurane or 1.3% halothane (end-tidal concentration). The PaCO2 was maintained between 35 and 45 mm of Hg by use of mechanical ventilation, and the following variables were determined: systolic, diastolic, and mean arterial blood pressures; cardiac output; cardiac index; stroke volume; heart rate; systemic vascular resistance; mean pulmonary arterial pressure; and pulmonary vascular resistance. In addition, arterial blood samples for gas and acid-base analyses were collected at 30-minute intervals for 2.5 hours. After baseline values were recorded, dogs were randomly assigned to receive either buprenorphine (16 micrograms/ kg, i.v.) or isovolumetric 5% dextrose solution. All variables were then recorded at 15-minute intervals for 2.5 hours. RESULTS: During isofl urane anesthesia, buprenorphine administration caused signifi cant (P < or = 0.05) reductions in diastolic arterial pressure, mean arterial pressure, systolic arterial pressure, cardiac index, and heart rate, whereas systemic vascular resistance increased signifi cantly. During halothane anesthesia, buprenorphine administration caused signifi cant decreases in heart rate, cardiac index, mean, systolic and diastolic arterial blood pressures, and stroke volume, whereas pulmonary arterial blood pressure and systemic vascular resistance increased signifi cantly. CONCLUSION: Although the changes seen were signifi cant, they were not suffi ciently large to be of clinical importance in healthy dogs.

5 je určen pro kočky i psy 3) Bylo zjištěno, že karprofen a buprenorfin byla dobře tolerovaná analgetika pro pětidenní podávání u koček. Naopak levometadon způsoboval v použitých dávkovacích schematech u některých koček centrální excitaci. Möllenhoff A, Nolte I, Kramer S. J Vet Med A Physiol Pathol Clin Med May;52(4): Anti-nociceptive efficacy of carprofen, levomethadone and buprenorphine for pain relief in cats following major orthopaedic surgery. A placebo-controlled, randomized blind study was conducted in cats (n = 60) after fracture repair to compare the analgesic effects as well as the side-effects of carprofen, buprenorphine and levomethadone during a 5-day treatment. Cats with severe shock symptoms or increases in blood urea nitrogen (BUN) and creatinine were excluded from the study. The cats were randomly assigned to four groups (n= 15). In group 1, carprofen was administered upon extubation at an initial dose of 4 mg/kg body weight, followed by one-third of that dose three times daily on days 2 to 5. In group 2, buprenorphine was administered in a single dose of 0.01 mg/kg body weight upon extubation and subsequently every 8 h. Levomethadone (group 3) was applied according to the same scheme at a dosage of 0.3 mg/kg body weight each time. The placebo (group 4) was given at the same time intervals as the opioids. Examinations were carried out prior to anaesthesia, between 30 min and 8 h after extubation, and on the following 4 days, 1 h after administration of the analgesics or the placebo as well as 1 h before the next administration. Pain and sedation evaluation was carried out with a visual analogue system (VAS) and with the aid of a numerical estimation scale (NRS). Pain was also scored by measuring mechanical nociceptive threshold of traumatized tissue. Plasma glucose and cortisol concentration, heart rate, respiration rate, blood pressure and body temperature were measured. Furthermore, a complete blood count and clinical chemistry including BUN, creatinine, alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), arterial blood pressure (AP), total protein and electrolytes of the cats were checked on the day of admission as well as on the last day of this study (day 5). Defaecation and urination as well as wound healing were monitored. On the basis of the mechanical nociceptive threshold of the traumatized tissue, concentrations of plasma glucose and cortisol and pain assessment using NRS and VAS, carprofen was found to have better anti-nociceptive effi cacy when compared with the two opioid analgesics, while the analgesic effect of levomethadone was similar to that of buprenorphine. However, the carprofen group also showed comparably high median NRS and VAS pain scores in addition to occasional broad deviations from the group mean on the fi rst post-operative treatment day. Sedative effects were detected for buprenorphine and levomethadone; in addition, symptoms of central excitation were noted with levomethadone. There was no indication of any clinically relevant respiratory depressive or cardiovascular effects, nor of any undesired renal, gastrointestinal or hepatic effects of the analgesics applied. However, the somewhat insensitive examination methods did not permit suffi cient evaluation of side-effects, particularly on the gastrointestinal tract and the kidneys. It was found that carprofen and buprenorphine were well-tolerated analgesics for a 5-day administration in the cat, whereas levomethadone caused central excitation in some cases in the dosage scheme used here. However, it was apparent that none of the tested analgesics induced suffi cient analgesia in the post-operative phase. For this reason, suitable methods must be found to improve analgesia, particularly in the immediate post-operative phase. 1) může být používán se širokým spektrem léčiv pro premedikaci a anestezii. V kombinacích je často možno snížit dávky ostatních léčiv. Buprenorfin může potencovat účinek centrálně účinkujících léčiv, avšak sám má v klinických dávkách pouze malý sedativní efekt (obdobně jako většina opiátů). SPC: When administered for potentiation of sedation or as part of premedication, the dose of other centrally-acting agents, such as acepromazine or medetomidine, should be reduced. The reduction will depend on the degree of sedation required, the individual animal, the type of other agents included in premedication and how anaesthesia is to be induced and maintained. It may Premedikace: dexmedetomidin 5 mcg/kg + buprenorfi n 10 mcg/kg, i.v. v jedné stříkačce. also be possible to reduce the amount of inhalational anaesthetic used. Buprenorphine has been used with acepromazine, alphaxalone/ alphadalone, atropine, dexmedetomidine, halothane, isofl urane, ketamine, medetomidine, propofol, sevofl urane, thiopentone and xylazine. When used in combination with sedatives, depressive effects on heart rate and respiration may be augmented. 2) Buprenorfin s dexmedetomidinem pro premedikaci před indukcí anestezie u psů. 31 psů. Indukce anestezie: za 5 min propofol i.v. do efektu (1-3 mg/kg) Udržování anestezie: izofl uran + dexmedetomidin CRI Dexmedetomidin podávaný konstantní rychlostí v infuzi je při anestezii psů (třídy ASA I-II) izofluranem hodnotným prvkem v udržování chirurgické anestezie. Studie prokázala adekvátní celkovou perfuzi tkání a nízké požadavky na dávku izofluranu. Probouzení po podání atipamezolu bylo hladké a rychlé. Uilenreef JJ, Murrell JC, McKusick BC, Hellebrekers LJ. Vet Anaesth Analg Jan;35(1):1-12. Dexmedetomidine continuous rate infusion during isoflurane anaesthesia in canine surgical patients OBJECTIVE: To determine the effects of three rates of dexmedetomidine (DMED) constant rate infusion (CRI) on overall tissue perfusion, isofl urane (ISO) requirements, haemodynamics and quality of recovery in canine surgical patients. STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: Client-owned dogs presented for soft tissue or orthopaedic surgery. METHODS: Following intravenous (IV) pre-medication with DMED (5 microg kg(-1)) and buprenorphine (10 microg kg(-1)) and propofol induction, anaesthesia was maintained with ISO in oxygen/air supplemented with a DMED CRI (1, 2 or 3 microg kg(-1) hour(-1); groups 1, 2 and 3, respectively). Ventilation was controlled in all animals using intermittent positive pressure ventilation (IPPV). Monitoring included end-tidal (ET) gases, ECG, arterial blood pressure, body temperature and sequential arterial blood gas and lactate measurements. Quality of recovery was scored after intramuscular (IM) administration of atipamezole (ATI) (12.5 microg kg(-1)). Immediate post-operative analgesia was provided with carprofen and/or buprenorphine. An analysis of variance was conducted for repeated measurements obtained during 80 minutes after fi rst incision. Categorical data were evaluated with Chi-square analyses. RESULTS: Arterial blood pressure remained stable and within clinically acceptable limits. Mean heart rate in group 2 was signifi cantly lower than in group 1. The incidence of 2nd degree AV block type II was signifi cantly higher in group 3. Mean arterial lactate concentrations remained below 2 mmol/l in all groups during the study, with a signifi cant increase occurring during recovery compared with surgery for group 3. Mean e ISO% was similar and <1% in all groups. Complete recovery from anaesthesia was achieved after ATI administration and was of good quality in all but three animals. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine CRI is a reliable and valuable adjunct to ISO anaesthesia in maintaining surgical anaesthesia in ASA I-II dogs. Data reported indicate adequate overall tissue perfusion and a low ISO requirement while enabling a smooth and rapid recovery following ATI. The DMED CRI of 1 microg kg(-1) hour(-1) following a loading dose of 5 microg kg(-1) produced the most favourable results. 3) Buprenorfin s dexmedetomidinem pro premedikaci před indukcí anestezie u psů. 60 psů. Premedikace, 3 skupiny: 1) 15 mcg/kg buprenorfi nu s 0,03 mg/kg acepromazinu, i.m. 2) 15 mcg/kg buprenorfi nu s 62,5 mcg/m2 dexmedetomidinu i.m. 3) 15 mcg/kg buprenorfi nu s 125 mcg/m2 dexmedetomidinu i.m. Indukce anestezie: po 30 min propofol do efektu Závěr: dávka propofolu nutná pro indukci anetezie byla u psů premedikovaných kombinací buprenorfi n + dexmedetomidin 125 mcg/m 2 ve srovnání s acepromazinem nižší.

6 Published as meeting abstracts Bell A, Pawson P, Auckburally A, Flaherty D. Abstract from WCVA aug-4 Sep, Glasgow, UK, p54. A comparison of dexmedetomidine and acepromazine in combination with buprenorphine as premedication prior to propofol target controlled induction of anaesthesia in dogs. 60 dogs (ASA I/II) were randomly allocated to recive 15 micg/kg buprenorphine combined with either 0.03 mg/kg acepromazine, 62,5 micg/m2 dexmedetomidine or 125 micrg/m2 dexmedetomidine i.m. After 30 minutes anaesthesia was induced using propofol target controlled infusion administered to effect. 6) V této studii testující teplotní nocicepci byl analgetický efekt dosažený kombinací lepší než analgetický efekt každého léčiva samostatně, bez ohledu na jeho dávku. 12 koček. B10) buprenorfi n 10 mcg/kg B20) buprenorfi n 20 mcg/kg D20) dexmedetomidin 20 mcg/kg D40) dexmedetomidin 40 mcg/kg B10)D20: buprenorfi n 10 mcg/kg + dexmedetomidin 20 mcg/kg 4) Buprenorfin s dexmedetomidinem byly používány pro zlepšení sedace u psů. Nicméně v této studii jsme nedosáhli pro buprenorfin dobrých výsledků. Důvodem může být zahájení operativního výkonu příliš brzy (za 20 min po intramuskulární aplikaci buprenorfinu), přičemž analgetický účinek buprenorfinu nastupuje později. Published as meeting abstracts Slingsby LS, Taylor PM, Waterman-Pearson AE. Abstract: AVA-ECVA, 7-10th March, 2007, Paris. Antinoceiception to a thermal stimulus in the cat: combination of dexmedetomidine with buprenorphine. 12 adult cats in randomised, crossover, blinded study in 5 groups of 6. Feline thermal nociceptive threshold testing device used. Leppänen MK, McKusick BC, Granholm MM, Westerholm FC, Tulamo R, Short CE. J Small Anim Pract Nov;47(11): Clinical efficacy and safety of dexmedetomidine and buprenorphine, butorphanol or diazepam for canine hip radiography. Santos LCP, Ludders JW, Gleed RD, Erb HN, Basher KM, Kirch P Abstract: PROCEEDINGS, MEETING OF THE AMERICAN COLLEGE OF VETERINARY ANESTHESIO- LOGISTS, September 10, 2009, Chicago, Illinois SEDATIVE AND CARDIORESPIRATORY EFFECTS OF DEX- MEDETOMIDINE AND BUPRENORPHINE ADMINISTE- RED TO CATS VIA ORAL TRANS-MUCOSAL OR INTRA- MUSCULAR ROUTES College of Veterinary Medicine, Cornell University, Ithaca, NY, USA Introduction: The objective was to evaluate whether the oral trans-mucosal (OTM) route of administration produced similar sedation to the intramuscular (IM) route for dexmedetomidine (20ug kg-1) plus buprenorphine (20ug kg-1) in cats being catheterized by veterinary students. Methods: Eighty-seven shelter-owned cats aged 5-48 months old, scheduled for ovariohysterectomy were randomly assigned OBJECTIVES: To investigate the usefulness of dexmedetomidine for restraint and sedation during hip radiographic examination of hip-extended or stress-radiography views when combined with either buprenorphine, butorphanol or diazepam. METHODS: One hundred and twenty-seven client-owned clinically healthy golden retrievers or rottweilers were enrolled in a clinical trial that compared hip-extended and PennHIP methods for diagnosing hip dysplasia and were randomly allocated to receive dexmedetomidine or medetomidine in combination with buprenorphine, butorphanol or diazepam. Subjective assessments were made for response to pain, response to noise, palpebral refl ex, muscle tone and overall quality of sedation; non-invasive physiological variables were also recorded. RESULTS: Overall quality of sedation was graded as good or excellent for dogs administered with a combination of butorphanol or diazepam. However, more dogs that received a combination involving buprenorphine had overall a relatively poorer quality of sedation and required additional administration of buprenorphine before the radiographic procedure could commence. Once sedated, clinically suffi cient muscle relaxation accompanied by a very low proportion of dogs responding to pain or noise stimuli were observed in all treatment groups. Heart and respiratory rate, and procedure and recovery times were similar for all treatment groups, and no adverse events were observed during the study. CLINICAL SIGNIFICANCE: Dexmedetomidine sedative protocols, particularly in combination with butorphanol and diazepam, can be used effectively and safely in dogs for radiographic procedures. 5) Dexmedetomidin a buprenorfin mohou být používány u koček dohromady. 87 koček. Sedace, 2 skupiny: 1) 20 mcg/kg buprenorfi nu + 20 mcg/kg dexmedetomidinu p.o. 2) 20 mcg/kg buprenorfi nu + 20 mcg/kg dexmedetomidinu i.m to one of the two treatments: OTM or IM. Heart rate, respiratory rate, and systolic arterial pressure were recorded before and 20 minutes after drug administration. At the time of catheter placement, posture, response to clipper sound, response to clipping, and response to restraint were scored by a blinded observer who also decided if ketamine (5mg kg-1, IM) was needed for successful catheterization. The signifi cance of differences was measured within treatment groups using the Wilcoxon signed-rank test and between treatment groups using the Wilcoxon Rank-sum test. Signifi cance was set at p<0.05. Results: Cats in the IM group were more likely to maintain lateral recumbency, to be amenable to restraint, and to be less responsive to clipper sound and clipping. The need for rescue sedation did not differ between the two groups; eighteen of eighty-seven cats required ketamine; seven (16%) in the IM group and eleven (25%) in the OTM group. Heart and respiratory rates declined after drug administration, at which time heart rate was lower in the IM group. No differences in blood pressure were detected. Conclusions: Although OTM provided signifi cantly less sedation than IM, it provided enough effect to allow an IV catheter to be placed in 75% of the cats. 7) Přidání buprenorfinu k medetomidinu při premedikaci u koček následně snižuje dávky jakéhokoli inhalačního anestetika. Nicméně, dávka propofolu potřebná k indukci anestezie se mezi jednotlivými skupinami nelišila. 40 koček. Premedikace, 4 skupiny: 1) 30 mcg/kg medetomidinu i.m. 2) 10 mcg/kg medetomidinu + 20 mcg/kg buprenorfi nu i.m. 3) 30 mcg/kg medetomidinu + 20 mcg/kg buprenorfi nu i.m. 4) 50 mcg/kg medetomidinu + 20 mcg/kg buprenorfi nu i.m. medetomidin + buprenorfi n smíchaný ve stříkačce okamžitě po premedikaci meloxikam 0,3 mg/kg s.c. Indukce anestezie: po 30 min bylo provedeno skórování sedace. Indukce proporfol i.v., Grint NJ, Burford J, Dugdale AH. J Small Anim Pract Feb;50(2): Investigating medetomidine-buprenorphine as preanaesthetic medication in cats. Division of Veterinary Anaesthesia, University of Liverpool, Leahurst, Neston, Wirral CH64 7TE, UK. Comment in: J Small Anim Pract Jul;50(7):378; author reply OBJECTIVES: The objective of this study was to investigate medetomidine-buprenorphine preanaesthetic medication in cats. METHODS: Forty American Society of Anesthesiologists (ASA) I female cats were enrolled in this prospective, blinded, clinical study. Cats were randomised into one of four groups: group M30 were injected intramuscularly with 30 microg/kg medetomidine, groups M10+B, M30+B and M50+B received 10, 30 and 50 Dávky propofolu (medián) mg/kg (rozsah) 1) 3,5 mg/kg propofolu (1,4-6 mg/kg) 2) 1,82 mg/kg propofolu (1-4 mg/kg) 3) 1,57 mg/kg propofolu (0,83-4 mg/kg) 4) 2 mg/kg propofolu (0-4 mg/kg) Udržování anestezie: izofl uran Postoperačně: inhalační anestetikum ukončeno a byl aplikován atipamezol (Antisedan) i.m.: 1) 0,075 mg/kg atipamezolu 3) 0,075 mg/kg atipamezolu 2) 0,025 mg/kg atipamezolu 4) 0,125 mg/kg atipamezolu microg/kg of medetomidine, respectively, each in combination with 20 microg/kg buprenorphine. After 30 minutes, a sedation score was allocated. Anaesthesia was induced using intravenous propofol and maintained using isofl urane in oxygen, while cats underwent ovariohysterectomy. Heart rate, respiratory rate, endtidal carbon dioxide tension and oxygen saturation of haemoglobin were recorded. Atipamezole was administered intramuscularly at volatile agent discontinuation. Time taken to lift their head, sit in sternal and stand were recorded along with quality of recovery. RESULTS: M30+B cats required signifi cantly less isofl urane compared with M30 cats. Heart rate and oxygen saturation of haemoglobin were signifi cantly lower in M50+B cats than in M30 cats. All M+B groups experienced signifi cantly better recoveries compared with the medetomidine only M30 control group. CLINICAL SIGNIFICANCE: The addition of buprenorphine to medetomidine preanaesthetic medication in cats reduces volatile agent vaporiser setting and improves the quality of recovery from anaesthesia.

7 8) Buprenorfin může být používán s medetomidinem pro sedaci psů. V této studii se jako vhodný protokol pro minoritní diagnostické zákroky u zdravých psů jevilo dávkování medetomidin 20 mcg/kg + buprenorfin 10 mcg/kg. Jestliže lze očekávat větší bolestivost zákroku, je doporučitelné zvýšit dávku medetomidinu na 30 mcg/kg. 10) Buprenorfin, resp. karprofen poskytují vyhovující postoperativní analgezii po prvních 6 hodin, resp. za 24 hodin po ovariohysterektomii u psů. Jestliže bylo třeba potencování analgezie, byla aplikována druhá dávka buprenorfinu. 60 psů. Sedace, 3 skupiny: 1) 10 mcg/kg buprenorfi nu + 10 mcg/kg medetomidinu i.m. 2) 10 mcg/kg buprenorfi nu + 20 mcg/kg medetomidinu i.m. 3) 10 mcg/kg buprenorfi nu + 30 mcg/kg medetomidinu i.m. Robinson KJ, Jones RS, Cripps PJ. J Small Anim Pract Sep;42(9): Effects of medetomidine and buprenorphine administered for sedation in dogs. Department of Anaesthesia, University Clinical Departments, University of Liverpool. Medetomidine at doses of 10, 20 or 30 microg/kg was administered along with 10 microg/kg buprenorphine intramuscularly to 48 dogs requiring sedation for various diagnostic or therapeutic Premedikace, 3 skupiny: B) 10 mcg/kg buprenorfi nu i.m. C) 4 mg/kg karprofenu s.c. BC) 10 mcg/kg buprenorfi nu i.m. + 4 mg/kg karprofenu s.c. Anestezie: 30 minut později: 80 mcg/kg medetomidinu + 7,5 mg/ kg ketaminu smícháno v jedné stříkačce i.m. Reverze: atipamezol 200 mcg/kg i.m. Anestezie: 24 případů potřebovalo pro provedení zákroku celkovou anestezii (thiopental 3,1 mg/kg) Reverze: Atipamezol i.m v pětinásobné dávce medetomidinu. Trval-li zákrok déle, nebo byla-li použita celková anestezie, dávky atipamezolu byly sníženy. Doby zotavení byly v této studii delší než dříve zaznamenané, pravděpodobně jako následek použití buprenorfi nu. procedures. The heart rate, respiratory rate and degree of sedation were recorded before and 30 minutes after administration of the drugs. Heart rate fell by a mean of 55 per cent and respiratory rate by a mean of 62 per cent. Mean sedation scores were increased in all groups. Administration of atipamezole at the end of the period of sedation produced rapid recoveries, with a mean time to standing of 12 minutes. Animals that were anaesthetised required much less thiopentone than the 10 mg/kg recommended after premedication with acepromazine maleate. 9) Buprenorfin a karprofen pro postoperativní analgezii u koček po ovariohysterektomii, anestezie kombinací medetomidin + ketamin. 84 koček. Multimodální analgezie by měla být zvažována i pro takové chirurgické zákroky, které mohou způsobit pouze slabší až střední bolestivost. Premedikace, 3 skupiny: Všechna zvířata dostala acepromazin 0,05 mg/kg C) 4 mg/kg karprofenu s.c. B) 20 mcg/kg buprenorfi nu i.m. B) 20 mcg/kg buprenorfi nu i.m. + 4 mg/kg karprofenu s.c. Shih AC, Robertson S, Isaza N, Pablo L, Davies W. Vet Anaesth Analg Jan;35(1): Comparison between analgesic effects of buprenorphine, carprofen, and buprenorphine with carprofen for canine ovariohysterectomy. Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville , USA. OBJECTIVE: To compare the analgesic effects of buprenorphine, carprofen, and their combination in dogs undergoing ovariohysterectomy. STUDY DESIGN: Prospective, randomized blinded clinical study. ANIMALS: 60 dogs. METHODS: Treatments were buprenorphine 0.02 mg kg(-1), intramuscularly (IM) (group B); carprofen 4 mg kg(-1), subcutaneously (SC) (group C); or a combination of both (group CB). Anesthesia was induced with propofol and maintained with isofl urane. A Dynamic Interactive Visual Analog Scale (DIVAS, mm) and the Glasgow Composite Pain Scale (GCMPS, 0-24) were used to evaluate comfort and sedation at baseline, 2, 4, 6, and 24 hours after extubation. Rescue analgesia was provided with buprenorphine (0.02 mg kg(-1)). Indukce anestezie: C): propofol 5.0 ± 1.4 mg/kg B): propofol 3.3 ± 1.1 mg/kg BC): propofol 3.2 ± 0.7 mg/kg Udržování anestezie: izofl uran Wound swelling measurements (WM) and a visual infl ammation score (VIS) of the incision were made after surgery and 2, 4, 6, and 24 hours later. p < 0.05 was considered signifi cant. RE- SULTS: Group C required more propofol (5.0 +/- 1.4 mg kg(-1)) compared with B (3.3 +/- 1.1 mg kg(-1)) and CB (3.2 +/- 0.7 mg kg(-1)); respectively, p = and Rescue analgesia was required in nine dogs. B had a higher GCMPS and DIVAS III score at 6 hours (2.6 +/- 2.5) and (23 +/ mm) compared with C (1.0 +/- 1.3, 6 +/- 7.3 mm) and CB (1.5 +/- 1.4, 8 +/ mm); respectively, p = 0.02 and Group C had a lower sedation score at 2 hours (43 +/ mm) compared with B (68 +/ mm) and BC (69 +/ mm); respectively, p = 0.03 and Group B had a higher WM score at 2 hours (3 +/- 0.8 mm) compared with C (2 +/- 0.6 mm) p = 0.01 and at 6 hours (3 +/- 1 mm) compared with C (2 +/- 0.8 mm) and CB (2 +/- 0.8 mm); respectively, p = 0.01 and VIS was not different between groups. CONCLUSION AND CLINICAL RE- LEVANCE: All treatments provided satisfactory analgesia for the fi rst 6 hours and at 24 hours. C and CB pain score and WS were superior to B at 6 hours. No superior analgesic effect was noted when the drugs were combined. Steagall PV, Taylor PM, Rodrigues LC, Ferreira TH, Minto BW, Aguiar AJ. Vet Rec Mar 21;164(12): Analgesia for cats after ovariohysterectomy with either buprenorphine or carprofen alone or in combination. Department of Surgery and Veterinary Anaesthesiology, School of Veterinary Medicine and Animal Science, FMVZ, UNESP, Botucatu, SP, Brazil. Eighty-four female cats undergoing ovariohysterectomy in a blinded, randomised, prospective clinical study were assigned to one of three groups of 28 to receive either 0.01 mg/kg buprenorphine (group B), 4 mg/kg carprofen (group C), or the same doses of both drugs (group BC). A dynamic and interactive visual analogue scale (DIVAS) from 0 to 100 mm, and a simple descriptive scale (SDS) from 0 to 4 were used to evaluate the cats degree of analgesia and sedation for 24 hours postoperatively. There was no signifi cant difference in the cats sedation scores by SDS or DIVAS, and no difference in their pain scores by DIVAS. By SDS, the cats in group BC had signifi cantly lower pain scores than the cats in group C (P<0.001) and group B (P<0.05). Nine of the cats in group B, nine in group C and fi ve in group BC required rescue analgesia, and the cats in group C required rescue earlier than those in group B (P<0.05).

8 může být aplikován intramuskulárně nebo intravenozně injekční roztok pro psy a kočky (buprenorphinum 0,3 mg/ml) 10 ml 1) Intravenozní premedikace medetomidinem (10 mcg/kg) a buprenorfinem (0.01 mg/kg) indukovala u psů během 5 min dobrou až výbornou sedaci. Rauser, P.; Lexmaulova, L ACTA VET.BRNO 2002, 71: Clinical comparison of medetomidine-butorphanol and medetomidine-buprenorphine combinations for intravenous premedication of general anaesthesia in the dog English Abstract We compared the effects of medetomidine (10 microg/kg) with butorphanol (0.1 mg/kg) and medetomidine (10 microg/kg) with buprenorphine (0.01 mg/kg) used for intravenous premedication of general anaesthesia during surgical procedures in clinical practice. The combination of alpha-adrenergic substances and opioids induced within 5 min good or moderately good sedation. Anaesthesia was induced by intravenous administration of propofol to achieve loss of laryngeal refl ex. General anaesthesia was maintained by a mixture of 02/N20/halothane and, at moments of insuffi cient depth of anaesthesia, it was intensifi ed by propofol re-administration. There was no difference in the dose of propofol for anaesthesia induction between above-mentioned combinations used for premedication. The number of re-administration and the total dose of propofol re-administered were signifi cantly (P 0,05) lower when premedicating by buprenorphine. We found neither differences in respiratory and heart rates, nor in Sp02. We found signifi cant (P 0.05) differences in ETCO2 values at the end of anaesthesia, when its concentration was higher in dogs premedicated by the combination of medetomidine-buprenorphine. Availability IAFI/CZ (Czech Republic), Availability number Serial Title Acta Veterinaria (Czech Republic), Serial ID - ISSN Serial number v. 71(1) p , Serial Date (Mar 2002) Po otevření spotřebujte do 28 dnů. 1. JMÉNO A ADRESA DRŽITELE ROZHODNUTÍ O REGISTRACI A DRŽITELE POVOLENÍ K VÝROBĚ ODPOVĚDNÉHO ZA UVOLNĚ- NÍ ŠARŽE, POKUD SE NESHODUJE Držitel rozhodnutí o registraci: Reckitt Benckiser Healthcare (UK) Ltd., Dansom Lane, Hull, HU8 7DS, U.K. Držitel(é) povolení k výrobě: Vericore Limited, Kinnoull Road, Kingsway West, Dundee, Tayside DD2 3XR, UK Reckitt Benckiser Healthcare (UK) Ltd., Dansom Lane, Hull, HU8 7DS, UK 2. NÁZEV VETERINÁRNÍHO LÉČIVÉHO PŘÍPRAVKU, 0,3 mg/ml injekčního roztoku pro psy a kočky Buprenorphinum ve formě Buprenorphini hydrochloridum 3. OBSAH LÉČIVÝCH A OSTATNÍCH LÁTEK 1 ml injekčního roztoku obsahuje: Léčivá látka: Buprenorphinum 0,3 mg ve formě Buprenorphini hydrochloridum 0,324 mg Pomocné látky: Chlorokresol 1,35 mg jako antimikrobiální přísada Čirý bezbarvý injekční roztok 4. INDIKACE se podává k úlevě pooperační bolesti u psů a koček a k zesílení sedativního účinku centrálně působících účinných látek u psů. 5. KONTRAINDIKACE Nepodávejte intratekálně nebo peridurálně. Nepoužívejte před provedením císařského řezu. 6. NEŽÁDOUCÍ ÚČINKY U psů se může vyskytnout slinění, bradykardie, hypotermie, třes, dehydratace a mióza. Vzácně pak hypertenze a tachykardie. U koček se často vyskytuje mydriáza a známky euforie (nepřiměřené vrnění, přecházení, tření), které obvykle odezní během 24 hodin. Buprenorfi n může vyvolat respiratorní depresi. Pokud je přípravek použit za účelem analgezie, dochází k sedativním účinkům velmi zřídka, ale tyto účinky se mohou vyskytnout, jestliže jsou podané dávky vyšší, než je doporučeno. Jestliže zaznamenáte jakékoliv závažné nežádoucí účinky či jiné reakce, které nejsou uvedeny v této příbalové informaci, oznamte to prosím svému veterinárnímu lékaři. 7. CÍLOVÝ DRUH ZVÍŘAT Psi a kočky 8. DÁVKOVÁNÍ PRO KAŽDÝ DRUH, CESTA(Y) A ZPŮSOB PODÁNÍ Před použitím důkladně protřepte. K aplikaci musí být použita vhodně dělená injekční stříkačka, aby bylo možné odměřit přesnou dávku. 9. POKYNY PRO SPRÁVNÉ PODÁNÍ Sedativní účinek se projevuje do 15 minut po podání, analgetický účinek nastupuje asi po 30 minutách. Aby byla analgezie během operace a ihned po probuzení účinná, měl by být přípravek podáván před operací jako součást premedikace. Pokud je následně nutná dodatečná analgezie, je možné aplikovat další dávku (dávky) buprenorfi nu nebo současně podat vhodné injekčně aplikované nesteroidní protizánětlivé léky (NSAID). Pokud je přípravek podáván pro zesílení sedace nebo jako součást premedikace, měla by být snížena dávka jiných centrálně působících účinných látek, například acepromazinu nebo medetomidinu. Snížení dávky závisí na stupni požadované sedace, zvířeti, typu dalších látek použitých k premedikaci a na tom, jakým způsobem je anestézie navozena a udržována. Také je možné snížit množství použitých inhalačních anestetik. 10. OCHRANNÁ LHŮTA Není určeno pro potravinová zvířata. 11. ZVLÁŠTNÍ OPATŘENÍ PRO UCHOVÁVÁNÍ Uchovávat mimo dosah dětí. Uchovávejte při teplotě do 25 C Uchovávejte lahvičku ve vnějším kartónovém obalu, aby byla chráněna před světlem. Před použitím důkladně protřepte. Nepoužívejte po uplynutí doby použitelnosti uvedené na etiketě. Doba použitelnosti po prvním otevření vnitřního obalu: 28 dní 12. ZVLÁŠTNÍ UPOZORNĚNÍ Bezpečnostní opatření: Buprenorfi n může vyvolat respiratorní depresi a proto, stejně jako u ostatních opiátů, je třeba zvýšené opatrnosti při léčbě zvířat s oslabenými dýchacími funkcemi nebo zvířat, která užívají léky, jež mohou tlumit aktivitu dýchacího centra. V případě dysfunkce ledvin, srdce nebo jater nebo šoku zvyšuje použití tohoto přípravku možnost rizika. Ošetřující veterinární lékař by měl před použitím tohoto přípravku posoudit poměr prospěchu a rizika. Bezpečnost přípravku nebyla dostatečně hodnocena u klinicky oslabených koček. Buprenorfi n by měl být používán s opatrností u zvířat se sníženou funkcí jater, a to především při postižení biliárního traktu, vzhledem k tomu, že je účinná látka v játrech metabolizována, může být u těchto zvířat intenzita a doba jejího trvání ovlivněna. Bezpečnost buprenorfi nu nebyla prokázána u zvířat mladších 7 týdnů, a proto by měl veterinární lékař před použitím přípravku u těchto zvířat zhodnotit poměr prospěchu a rizika. Opakované podání v intervalu kratším než je doporučeno pro opakované podání v bodě 9 se nedoporučuje. Dlouhodobá bezpečnost podávání buprenorfi nu u koček nebyla hodnocena déle než 5 po sobě jdoucích dní. Účinek opiátů při zranění hlavy je závislý na druhu a vážnosti zranění a poskytnuté podpoře dýchání. Přípravek by měl být užíván až po zhodnocení poměru prospěchu a rizika ošetřujícím veterinárním lékařem. Kontakt pro objednávání vetergesic@orionpharma.cz Druhy Cesta podání Pooperační analgezie Zesílení sedace Psi Intramuskulární nebo intravenózní podání mikrogramů na kg (0,3 0,6 ml na 10 kg). Pokud je to nutné, opakujte aplikaci pro další úlevu od bolesti po 3 4 hodinách dávkou 10 mikrogramů na kg nebo po 5 6 hodinách dávkou 20 mikrogramů na kg mikrogramů na kg (0,3 0,6 ml na 10 kg) Kočky Intramuskulární nebo intravenózní podání mikrogramů na kg (0,3 0,6 ml na 10 kg).opakujte, pokud je to nutné, jednou po 1 2 hodinách. ---

9 injekční roztok pro psy a kočky (buprenorphinum 0,3 mg/ml) 10 ml Březost: Laboratorní studie na potkanech neprokázaly teratogenní účinky přípravku. Nicméně tyto studie prokázaly poimplantační ztráty a časné fetální úhyny.toto může být způsobeno snížením kondice rodičů během gestace a následkem sedace matek v době postnatální péče. Vzhledem k tomu, že studie toxicity na reprodukci nebyly uskutečněny u cílových druhů zvířat, použijte přípravek pouze po zvážení poměru prospěchu a rizika příslušným veterinárním lékařem. Tento přípravek by neměl být použit před provedením císařského řezu z důvodu rizika respiratorní deprese u mláďat během porodu. Měl by být se zvláštní opatrností použit pouze po zákroku. Laktace: Studie u laktujících potkanů prokázaly, že po intramuskulární aplikaci buprenorfi nu se koncentrace nezměněného buprenorfi nu v mléce vyrovnala nebo přesáhla jeho koncentraci v plazmě. Vzhledem k pravděpodobnosti vylučování buprenorfi nu mlékem i u jiných druhů zvířat se jeho užití během laktace nedoporučuje. Přípravek použijte pouze po zvážení poměru prospěchu a rizika příslušným veterinárním lékařem. Interakce s dalšími léčivými přípravky a další formy interakce: Buprenorfi n může vyvolat ospalost, která může být zesílena dalšími centrálně působícími účinnými látkami včetně utišujících prostředků, sedativ a hypnotik. Doporučuje se nepoužívat buprenorfi n společně s dalšími analgetiky morfi nového a opiátového typu, jako je např. etorfi n, fentanyl, petidin, metadon, papaverin nebo butorfanol, a to i přesto, že je u lidí prokázáno, že léčebné dávky buprenorfi nu nesnižují analgetický účinek standardních dávek opiátových antagonistů. Pokud je buprenorfi n použit v normálním léčebném rozsahu, mohou být standardní dávky opiátových antagonistů podávány před tím, než odezní vliv buprenorfi nu, aniž by došlo ke snížení analgezie. Buprenorfin je používán s acepromazinem, alfaxalonem/alfadalonem, atropinem, dexmedetomidinem, halotanem, isofluranem, ketaminem, medetomidinem, propofolem, sevofluranem, thiopentalem a xylazinem. Pokud je přípravek použit v kombinaci se sedativy, může být zesílen jejich tlumivý vliv na srdeční tep a dýchací funkce. Bezpečnost uživatele a varování: Po jakémkoli náhodném zasažení kůže si důkladně umyjte ruce a/nebo zasaženou oblast. Buprenorfi n má opioidní aktivitu, tzn. že při aplikaci je nutné dbát zvýšené opatrnosti, neporanit jiné osoby ani sebe. V případě náhodného samopodání injekce nebo pozření vyhledejte ihned lékařskou pomoc a ukažte příbalovou informaci nebo etiketu praktickému lékaři. Pokud dojde k zasažení oka nebo kontaktu s pokožkou, důkladně omyjte zasažené místo pod studenou tekoucí vodou. V případě přetrvávajícího podráždění vyhledejte lékařskou pomoc. Při prvním otevření krabice najděte datum spotřeby, které je uvedeno na vnitřním obalu užívaného přípravku a které uvádí, do kterého dne je třeba veškerý zbývající přípravek v této krabici vyřadit. Toto datum pro vyřazení přípravku by mělo být napsáno do volného místa na etiketě. Předávkování: V případě předávkování by měla být přijata podpůrná opatření a, pokud je to vhodné, lze použít naloxon nebo stimulanty dýchacího ústrojí. Při předávkování psů může buprenorfi n způsobit letargii. Při velmi vysokých dávkách se může vyskytnout bradykardie a mióza. Použití naloxonu je vhodné pro povzbuzení snížené dýchací aktivity. Stimulanty dýchacích funkcí, např. doxapram, jsou účinné i u člověka. Z důvodu prodlouženého účinku buprenorfi nu v porovnání s výše uvedenými léky je nutné, aby byly podávány opakovaně nebo průběžně v infuzi. Dobrovolné studie u člověka zjistily, že opiátoví antagonisté nemusí plně zvrátit účinek buprenorfi nu. V toxikologických studiích na buprenorfi n hydrochlorid u psů byla pozorována biliární hyperplazie po perorálním podávání přípravku po dobu 1 roku v dávce 3,5 mg/kg/den a vyšší. Biliární hyperplazie nebyla pozorována po každodenní intramuskulární aplikaci v dávce nad 2,5 mg/kg/den po dobu 3 měsíců. Tato dávka značně přesahuje jakémkoli klinické dávkovací schéma u psů. 13. ZVLÁŠTNÍ OPATŘENÍ PRO ZNEŠKODŇOVÁNÍ NEPOUŽITÝCH PŘÍPRAVKŮ NEBO ODPADU, POKUD JE JICH TŘEBA Všechen nepoužitý veterinární léčivý přípravek nebo odpad, který pochází z tohoto přípravku, musí být likvidován podle místních právních předpisů. 14. DATUM POSLEDNÍ REVIZE PŘÍBALOVÉ INFORMACE 10/ DALŠÍ INFORMACE Velikosti balení: 1 3,0 ml (1 stříkačka na obal) je obsažen v 10ml lahvičce z tmavého skla s chlorbutylovou gumovou zátkou ve formě sterilního, čirého, bezbarvého vodného roztoku pro injekce. V každém 1 ml jsou obsaženy 0,3 mg buprenorfi nu ve formě buprenorfi n hydrochloridu v 5 % roztoku glukózy. Přípravek také obsahuje 1,35 mg/ml chlorokresolu jakožto antimikrobiální přísady. Pouze na veterinární předpis. Distributor: Orion Oyj, organizační složka Zelený pruh 95/97, , Praha, ČR Tel.: , fax: Kompletní souhrn informací o přípravku najdete v příbalovém letáku. Orion Oyj organizační složka, Zelený pruh 95/97, Praha tel.: , fax: